Enhanced pulmonary and intestinal activation of procarcinogens and mutagens after chronic ethanol consumption in the rat.
Recent epidemiological surveys have indicated that alcoholics exhibit increased incidences of a variety of cancers. We have investigated, as a possible contributing factor to carcinogenesis in this population, the effect of chronic ethanol consumption on metabolic activation of procarcinogens by microsomes isolated from lungs and small intestine. These tissues are major sites through which procarcinogens enter the body and are also potential sites of procarcinogen metabolism. Rat litter-mates were pair-fed nutritionally adequate liquid diets which contained either ethanol as 36% of total energy or an equivalent energy content of carbohydrates in place of ethanol. Chronic ethanol consumption produced significant increases in pulmonary microsomal cytochrome P-450 and microsomal ethanol oxidation. The ethanol diet also enhanced the capacity of pulmonary microsomes to activate compounds present in tobacco pyrolyzates to mutagens detectable in the Ames Salmonella auxotroph reversion assay. The ethanol diet did not alter the capacity of pulmonary microsomes to hydroxylate benzo(a)pyrene (BaP) or to activate BaP to a mutagen. In contrast, microsomes from the upper small intestine of ethanol-fed rats did exhibit both higher levels of BaP hydroxylase activity and enhanced activation of BaP to a mutagen. The ethanol feeding also enhanced the capacity of the intestinal microsomes to activate to mutagens both tryptophan pyrolyzate and 2-aminofluorene but did not influence the metabolic activation of these promutagens by pulmonary microsomes. Chronic ethanol consumption thus influences carcinogen metabolism in the intestine and lung in a manner which varies with respect to both carcinogen and tissue.
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D009153:Mutagens; D010936:Plant Extracts / Q000494:pharmacology; D010947:Plants, Toxic; D051381:Rats; D014026:Nicotiana; D014364:Tryptophan / Q000494:pharmacology
D001580:Benzopyrenes; D002273:Carcinogens; D009153:Mutagens; D010936:Plant Extracts; D014364:Tryptophan; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase